Abstract
An association between the brain serotonin (5-HT) system and feeding has been postulated since the 1970s but it has only been in recent years that the nature of 5- HT-mediated hypophagia has become well understood, and the receptor subtypes responsible for the effect better defined. The invention and utilisation of subtypeselective 5-HT receptor antagonists has demonstrated that the 5-HT2C receptor is of paramount importance in this regard. Importantly, ethological studies of animal behaviour have shown that the hypophagia resulting from 5-HT2C receptor activation is likely to be a consequence of increased satiety and this is in contrast to hypophagia following 5-HT2A receptor activation. Furthermore, recent studies have also shown that 5-HT2C receptor agonists not only reduce feeding when acutely administered to rats or mice, they can also reduce body weight without inducing tolerance when administered chronically to obese animals. These observations have led researchers to conclude that selective 5- HT2C receptor agonists have the potential to be effective anti-obesity agents. Encouragingly, this suggestion is supported by both direct and indirect evidence from clinical studies. Indirect evidence stems from recent observations that the clinically effective anorectic agent d-fenfluramine exerts its hypophagic and weight-loss effects via 5-HT2C receptor activation. More direct clinical evidence derives from the use of the prototypical 5-HT2C receptor agonist m-chlorophenylpiperazine (mCPP), with which both acute hypophagia and body-weight loss have been observed. The current paper therefore reviews both the pre-clinical and clinical evidence supporting the use of 5-HT2C receptor agonists for the treatment of obesity and assesses the developments that have been made in this regard to date.
Keywords: 5-ht2c receptor, obesity, hypophagia, appetite, satiety
Current Topics in Medicinal Chemistry
Title: 5-HT2C Receptor Agonists as Potential Drugs for the Treatment of Obesity
Volume: 3 Issue: 8
Author(s): Michael J. Bickerdike
Affiliation:
Keywords: 5-ht2c receptor, obesity, hypophagia, appetite, satiety
Abstract: An association between the brain serotonin (5-HT) system and feeding has been postulated since the 1970s but it has only been in recent years that the nature of 5- HT-mediated hypophagia has become well understood, and the receptor subtypes responsible for the effect better defined. The invention and utilisation of subtypeselective 5-HT receptor antagonists has demonstrated that the 5-HT2C receptor is of paramount importance in this regard. Importantly, ethological studies of animal behaviour have shown that the hypophagia resulting from 5-HT2C receptor activation is likely to be a consequence of increased satiety and this is in contrast to hypophagia following 5-HT2A receptor activation. Furthermore, recent studies have also shown that 5-HT2C receptor agonists not only reduce feeding when acutely administered to rats or mice, they can also reduce body weight without inducing tolerance when administered chronically to obese animals. These observations have led researchers to conclude that selective 5- HT2C receptor agonists have the potential to be effective anti-obesity agents. Encouragingly, this suggestion is supported by both direct and indirect evidence from clinical studies. Indirect evidence stems from recent observations that the clinically effective anorectic agent d-fenfluramine exerts its hypophagic and weight-loss effects via 5-HT2C receptor activation. More direct clinical evidence derives from the use of the prototypical 5-HT2C receptor agonist m-chlorophenylpiperazine (mCPP), with which both acute hypophagia and body-weight loss have been observed. The current paper therefore reviews both the pre-clinical and clinical evidence supporting the use of 5-HT2C receptor agonists for the treatment of obesity and assesses the developments that have been made in this regard to date.
Export Options
About this article
Cite this article as:
Bickerdike J. Michael, 5-HT2C Receptor Agonists as Potential Drugs for the Treatment of Obesity, Current Topics in Medicinal Chemistry 2003; 3 (8) . https://dx.doi.org/10.2174/1568026033452249
DOI https://dx.doi.org/10.2174/1568026033452249 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Antigen-specific Immunotherapy in Ovarian Cancer and p53 as Tumor Antigen
Current Pharmaceutical Design The Neuroprotective Effects of Purslane (Portulaca oleracea) on Rotenone- Induced Biochemical Changes and Apoptosis in Brain of Rat
CNS & Neurological Disorders - Drug Targets Gene and Cancer Therapy - Pseudorabies Virus: A Novel Research and Therapeutic Tool?
Current Gene Therapy FoxO Proteins: Regulation and Molecular Targets in Liver Cancer
Current Medicinal Chemistry Gene Expression Analysis Approach to Establish Possible Links Between Parkinson's Disease, Cancer and Cardiovascular Diseases
CNS & Neurological Disorders - Drug Targets ADAM19/Adamalysin 19 Structure, Function, and Role as a Putative Target in Tumors and Inflammatory Diseases
Current Pharmaceutical Design Ribonucleases, Nucleases and Antiangiogenins in Antiproliferative Activities
Current Signal Transduction Therapy Targeting IGF-I, IGFBPs and IGF-I Receptor System in Cancer: The Current and Future in Breast Cancer Therapy
Recent Patents on Anti-Cancer Drug Discovery Critical Enzymes Involved in Endocannabinoid Metabolism
Protein & Peptide Letters Cannabis sativa L. Constituents and Their Role in Neuroinflammation
Current Bioactive Compounds Reversal of Tumor Induced Dendritic Cell Paralysis: A Treatment Regimen Against Cancer
Current Immunology Reviews (Discontinued) Antiproliferative Activity of microRNA-125a and its Molecular Targets
MicroRNA A MicroRNA-BDNF Negative Feedback Signaling Loop in Brain: Implications for Alzheimer’s Disease
MicroRNA Lipoxygenase Inhibitors as Cancer Chemopreventives: Discovery, Recent Developments and Future Perspectives
Current Medicinal Chemistry A Review of Neuroprotective Agents
Current Medicinal Chemistry Methionine Aminopeptidases as Potential Targets for Treatment of Gastrointestinal Cancers and other Tumors
Current Drug Targets Survivin: Role in Normal Cells and in Pathological Conditions
Current Cancer Drug Targets Antioxidant Activity of Galantamine and Some of its Derivatives
Current Medicinal Chemistry Pharmacological Properties and Therapeutic Potential of Naringenin: A Citrus Flavonoid of Pharmaceutical Promise
Current Pharmaceutical Design Small Heat Shock Proteins and Protein-Misfolding Diseases
Current Pharmaceutical Biotechnology